Association of the intercellular adhesion molecule-1 (ICAM-1) gene polymorphisms with endometriosis: a systematic review and meta-analysis.

ABSTRACT

BACKGROUND: Reported associations of the G241R and K469E polymorphisms of the intercellular adhesion molecule-1 gene (ICAM-1) gene with endometriosis have differed in magnitude. MATERIALS AND METHODS: In a meta-analysis of six published case-control studies (from five articles), we estimated risk [odds ratio (OR) 95 % confidence intervals (CI)] of associations with these polymorphisms using the Review Manager 5.3 software. RESULTS: Based on 1213 cases and 1103 controls, overall analysis showed significant increased risk in the homozygous (OR 2.83, 95 % CI 0.99-8.10, p = 0.05), dominant (OR 1.86, 95 % CI 1.00-3.46, p = 0.05) and codominant (OR 2.15, 95 % CI 1.06-4.35, p = 0.03) models. Confined to the studies in Hardy-Weinberg Equilibrium erased the significance (OR 1.59-2.59, 95 % CI 0.81-8.22, p = 0.10-0.15). Asian effects were variable (OR 0.93-1.09, p = 0.50-0.57), but Caucasian effects were not (OR 4.09-13.60, p < 0.0001). Independent data for the late stages of endometriosis suggest protection of the ICAM-1 K469E polymorphism among the Asians (OR 0.91-0.95, p = 0.35-0.71). These effects were weak but non-heterogeneous (P heterogeneity = 0.17-0.57, I (2) = 0-40 %). CONCLUSION: In summary, strengths of the overall effects were consistency, significance and robustness but limited by their high heterogeneity. These strengths and limitations were also observed in the Caucasian subgroup which when tested for interaction against the contrasting Asian effects, highlighted Caucasian susceptibility (p = 0.004-0.01). The findings are an interplay of strengths and limitations, which warrant awareness of their interpretation as susceptibility markers for this disorder.